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Spinal Motoneurons (spinal + motoneuron)
Selected AbstractsMotoneurons: A preferred firing range across vertebrate species?MUSCLE AND NERVE, Issue 5 2002T. George Hornby PhD Abstract The term "preferred firing range" describes a pattern of human motor unit (MU) unitary discharge during a voluntary contraction in which the profile of the spike-frequency of the MU's compound action potential is dissociated from the profile of the presumed depolarizing pressure exerted on the unit's spinal motoneuron (MN). Such a dissociation has recently been attributed by inference to the presence of a plateau potential (PP) in the active MN. This inference is supported by the qualitative similarities between the firing pattern of human MUs during selected types of relatively brief muscle contraction and that of intracellularly stimulated, PP-generating cat MNs in a decerebrate preparation, and turtle MNs in an in vitro slice of spinal cord. There are also similarities between the stimulus-response behavior of intracellularly stimulated turtle MNs and human MUs during the elaboration of a slowly rising voluntary contraction. This review emphasizes that there are a variety of open issues concerning the PP. Nonetheless, a rapidly growing body of comparative vertebrate evidence supports the idea that the PP and other forms of non-linear MN behavior play a major role in the regulation of muscle force, from the lamprey to the human. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000,000, 2002 [source] Developmental characteristics of AMPA receptors in chick lumbar motoneuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2007Xianglian Ni Abstract Ca2+ fluxes through ionotropic glutamate receptors regulate a variety of developmental processes, including neurite outgrowth and naturally occurring cell death. In the CNS, NMDA receptors were originally thought to be the sole source of Ca2+ influx through glutamate receptors; however, AMPA receptors also allow a significant influx of Ca2+ ions. The Ca2+ permeability of AMPA receptors is regulated by the insertion of one or more edited GluR2 subunits. In this study, we tested the possibility that changes in GluR2 expression regulate the Ca2+ permeability of AMPA receptors during a critical period of neuronal development in chick lumbar motoneurons. GluR2 expression is absent between embryonic day (E) 5 and E7, but increases significantly by E8 in the chick ventral spinal cord. Increased GluR2 protein expression is correlated with parallel changes in GluR2 mRNA in the motoneuron pool. Electrophysiological recordings of kainate-evoked currents indicate a significant reduction in the Ca2+ -permeability of AMPA receptors between E6 and E11. Kainate-evoked currents were sensitive to the AMPA receptor blocker GYKI 52466. Application of AMPA or kainate generates a significant increase in the intracellular Ca2+ concentration in E6 spinal motoneurons, but generates a small response in older neurons. Changes in the Ca2+ -permeability of AMPA receptors are not mediated by age-dependent changes in the editing pattern of GluR2 subunits. These findings raise the possibility that Ca2+ influx through Ca2+ -permeable AMPA receptors plays an important role during early embryonic development in chick spinal motoneurons. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] N-cadherin is regulated by gonadal steroids in adult sexually dimorphic spinal motoneuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2001Douglas A. Monks Abstract Gonadal steroids influence the morphology and function of neurons in the adult spinal cord through cellular and molecular mechanisms that are largely unknown. The cadherins are cell adhesion molecules that participate in the formation and organization of the CNS during embryonic development, and recent evidence suggests that the cadherins continue to regulate neural structure and function in adulthood. Using degenerate oligonucleotides coding conserved regions of the catenin-binding domain of classical cadherins in a RT-PCR cloning strategy, we identified several cadherin subtypes, the most frequently cloned being N-, E-, and R-cadherin, suggesting that these are the major classical cadherin subtypes present in the adult male rat lumbosacral spinal cord. We then examined cadherin expression levels of these cadherin subtypes under steroid conditions known to induce plastic changes in spinal motoneurons. Semiquantitative PCR revealed that mRNA levels of N-cadherin, but not E-cadherin or R-cadherin, are elevated in castrated rats treated with testosterone, 17,-estradiol, or dihydrotestosterone relative to castrate rats not treated with steroids. Immunolocalization of N-cadherin revealed that steroid treatment increased N-cadherin expression levels in functionally related neural populations whose morphology and function are regulated by steroids. These results suggest a role for N-cadherin in steroid-induced neuroplastic change in the adult lumbar spinal cord. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 255,264, 2001 [source] Dedifferentiation of intrinsic response properties of motoneurons in organotypic cultures of the spinal cord of the adult turtleEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2000Jean-François Perrier Abstract Explant cultures from the spinal cord of adult turtles were established and used to study the sensitivity of the intrinsic response properties of motoneurons to the changes in connectivity and milieu imposed by isolation in culture. Transverse sections 700 ,m thick were explanted on cover slips and maintained in roller-tube cultures in medium containing serum and the growth factors brain-derived neurotrophin factor (BDNF), neurotrophin-3 (NT3), glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF). The gross morphology of acute sections was maintained after 4 weeks in culture. Cell bodies of motoneurons remained stainable in fixed cultures with an antibody against choline acetyltransferase (ChAT) throughout the culture period. During culture, motoneurons maintained stable resting membrane potentials and were contacted by functional synapses. The ability to generate action potentials was also preserved as was delayed inward rectification and generation of calcium spikes in the presence of tetra-ethyl ammonium (TEA). In response to depolarization, however, motoneurons presented strong outward rectification, and only 41% of the cells recorded from maintained the ability to fire repetitively. By the second week in culture, a fraction of motoneurons displayed fast and slow transient outward rectification and low-threshold calcium spikes, features not seen in turtle motoneurons in acute slices. On the other hand, properties mediated by L-type Ca2+ channels disappeared during the first few days in culture. Our observations show that the phenotypical intrinsic response properties of mature spinal motoneurons are modified in explant cultures. The properties acquired resemble the properties in juvenile motoneurons in several species of terrestrial vertebrates. [source] Dendritic L-type calcium currents in mouse spinal motoneurons: implications for bistabilityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2000K. P. Carlin Abstract The intrinsic properties of mammalian spinal motoneurons provide them with the capability to produce high rates of sustained firing in response to transient inputs (bistability). Even though it has been suggested that a persistent dendritic calcium current is responsible for the depolarizing drive underlying this firing property, such a current has not been demonstrated in these cells. In this study, calcium currents are recorded from functionally mature mouse spinal motoneurons using somatic whole-cell patch-clamp techniques. Under these conditions a component of the current demonstrated kinetics consistent with a current originating at a site spatially segregated from the soma. In response to step commands this component was seen as a late-onset, low amplitude persistent current whilst in response to depolarizing,repolarizing ramp commands a low voltage clockwise current hysteresis was recorded. Simulations using a neuromorphic motoneuron model could reproduce these currents only if a noninactivating calcium conductance was placed in the dendritic compartments. Pharmacological studies demonstrated that both the late-onset and hysteretic currents demonstrated sensitivity to both dihydropyridines and the L-channel activator FPL-64176. Furthermore, the ,1D subunits of L-type calcium channels were immunohistochemically demonstrated on motoneuronal dendrites. It is concluded that there are dendritically located L-type channels in mammalian motoneurons capable of mediating a persistent depolarizing drive to the soma and which probably mediate the bistable behaviour of these cells. [source] Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosisGLIA, Issue 2 2009Chrissandra J. Zagami Abstract In amyotrophic lateral sclerosis (ALS) non-neuronal cells play key roles in disease etiology and loss of motoneurons via noncell-autonomous mechanisms. Reactive astrogliosis and dysfunctional transporters for L -glutamate [excitatory amino acid transporters, (EAATs)] are hallmarks of ALS pathology. Here, we describe mechanistic insights into ALS pathology involving EAAT-associated homeostasis in response to a destructive milieu, in which oxidative stress and excitotoxicity induce respectively astrogliosis and motoneuron injury. Using an in vitro neuronal-glial culture of embryonic mouse spinal cord, we demonstrate that EAAT activity was maintained initially, despite a loss of cellular viability induced by exposure to oxidative [3-morpholinosydnonimine chloride (SIN-1)] and excitotoxic [(S)-5-fluorowillardiine (FW)] conditions. This homeostatic response of EAAT function involved no change in the cell surface expression of EAAT1/2 at 0.5,4 h, but rather alterations in kinetic properties. Over this time-frame, EAAT1/2 both became more widespread across astrocytic arbors in concert with increased expression of glial fibrillary acidic protein (GFAP), although at 8,24 h there was gliotoxicity, especially with SIN-1 rather than FW. An opposite picture was found for motoneurons where FW, not SIN-1, produced early and extensive neuritic shrinkage and blebbing (,0.5 h) with somata loss from 2 h. We postulate that EAATs play an early homeostatic and protective role in the pathologic milieu. Moreover, the differential profiles of injury produced by oxidative and excitotoxic insults identify two distinct phases of injury which parallel important aspects of the pathology of ALS. © 2008 Wiley-Liss, Inc. [source] Alsin/Rac1 signaling controls survival and growth of spinal motoneuronsANNALS OF NEUROLOGY, Issue 1 2006Arnaud Jacquier MSc Objective Recessive mutations in alsin, a guanine-nucleotide exchange factor for the GTPases Rab5 and Rac1, cause juvenile amyotrophic lateral sclerosis (ALS2) and related motoneuron disorders. Alsin function in motoneurons remained unclear because alsin knock-out mice do not develop overt signs of motoneuron degeneration. Methods To generate an alsin loss-of-function model in an ALS-relevant cell type, we developed a new small interfering RNA electroporation technique that allows efficient knock down of alsin in embryonic rat spinal motoneurons. Results After small interfering RNA,mediated alsin knockdown, cultured motoneurons displayed a reduced apparent size of EEA1-labeled early endosomes and an increased intracellular accumulation of transferrin and L1CAM. Alsin knockdown induced cell death in 32 to 48% of motoneurons and significantly inhibited axon growth in the surviving neurons. Both cellular phenotypes were mimicked by expression of a dominant-negative Rac1 mutant and were completely blocked by expression of a constitutively active Rac1 mutant. Expression of dominant-negative or constitutively active forms of Rab5 had no such effects. Interpretation Our data demonstrate that alsin controls the growth and survival of motoneurons in a Rac1-dependant manner. The strategy reported here illustrates how small interfering RNA electroporation can be used to generate cellular models of neurodegenerative disease involving a loss-of-function mechanism. Ann Neurol 2006;60:105,117 [source] | |||||||||||||